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Animal locomotion is the result of complex and multi-layered interactions between the nervous system, the musculo-skeletal system and the environment. Decoding the underlying mechanisms requires an integrative approach. Comparative experimental biology has allowed researchers to study the underlying components and some of their interactions across diverse animals. These studies have shown that locomotor neural circuits are distributed in the spinal cord, the midbrain and higher brain regions in vertebrates. The spinal cord plays a key role in locomotor control because it contains central pattern generators (CPGs) - systems of coupled neuronal oscillators that provide coordinated rhythmic control of muscle activation that can be viewed as feedforward controllers - and multiple reflex loops that provide feedback mechanisms. These circuits are activated and modulated by descending pathways from the brain. The relative contributions of CPGs, feedback loops and descending modulation, and how these vary between species and locomotor conditions, remain poorly understood. Robots and neuromechanical simulations can complement experimental approaches by testing specific hypotheses and performing what-if scenarios. This Review will give an overview of key knowledge gained from comparative vertebrate experiments, and insights obtained from neuromechanical simulations and robotic approaches. We suggest that the roles of CPGs, feedback loops and descending modulation vary among animals depending on body size, intrinsic mechanical stability, time required to reach locomotor maturity and speed effects. We also hypothesize that distal joints rely more on feedback control compared with proximal joints. Finally, we highlight important opportunities to address fundamental biological questions through continued collaboration between experimentalists and engineers.

Locomotion is a complex process involving specific interactions between the central neural controller and the mechanical components of the system. The basic rhythmic activity generated by locomotor circuits in the spinal cord defines rhythmic limb movements and their central coordination. The operation of these circuits is modulated by sensory feedback from the limbs providing information about the state of the limbs and the body. However, the specific role and contribution of central interactions and sensory feedback in the control of locomotor gait and posture remain poorly understood. We use biomechanical data on quadrupedal locomotion in mice and recent findings on the organization of neural interactions within the spinal locomotor circuitry to create and analyse a tractable mathematical model of mouse locomotion. The model includes a simplified mechanical model of the mouse body with four limbs and a central controller composed of four rhythm generators, each operating as a state machine controlling the state of one limb. Feedback signals characterize the load and extension of each limb as well as postural stability (balance). We systematically investigate and compare several model versions and compare their behaviour to existing experimental data on mouse locomotion. Our results highlight the specific roles of sensory feedback and some central propriospinal interactions between circuits controlling fore and hind limbs for speed-dependent gait expression. Our models suggest that postural imbalance feedback may be critically involved in the control of swing-to-stance transitions in each limb and the stabilization of walking direction.

[Display omitted] • Retrograde infection of somatosensory neurons via intraspinal rabies injection. • Anterograde tracing of postsynaptic spinal targets. • Stereotyped spatial organization of spinal neurons receiving input from distinct sensory modalities. Somatosensory neurons detect vital information about the environment and internal status of the body, such as temperature, touch, itch, and proprioception. The circuit mechanisms controlling the coding of somatosensory information and the generation of appropriate behavioral responses are not clear yet. In order to address this issue, it is important to define the precise connectivity patterns between primary sensory afferents dedicated to the detection of different stimuli and recipient neurons in the central nervous system. In this study we describe and validate a rabies tracing approach for mapping mouse spinal circuits receiving sensory input from distinct, genetically defined, modalities. We analyzed the anatomical organization of spinal circuits involved in coding of thermal and mechanical stimuli and showed that somatosensory information from distinct modalities is relayed to partially overlapping ensembles of interneurons displaying stereotyped laminar organization, thus highlighting the importance of positional features and population coding for the processing and integration of somatosensory information. [ABSTRACT FROM AUTHOR]

Primitive reflexes are evident shortly after birth. Many of these reflexes disappear during postnatal development as part of the maturation of motor control. This study investigates the changes of connectivity related to sensory integration by spinal dI3 interneurons during the time in which the palmar grasp reflex gradually disappears in postnatal mice pups. Our results reveal an increase in GAD65/67-labeled terminals to perisomatic Vglut1-labeled sensory inputs contacting cervical and lumbar dI3 interneurons between postnatal day 3 and day 25. In contrast, there were no changes in the number of perisomatic Vglut1-labeled sensory inputs to lumbar and cervical dI3 interneurons other than a decrease between postnatal day 15 and day 25. Changes in postsynaptic GAD65/67-labeled inputs to dI3 interneurons were inconsistent with a role in the sustained loss of the grasp reflex. These results suggest a possible link between the maturation of hand grasp during postnatal development and increased presynaptic inhibition of sensory inputs to dI3 interneurons. [ABSTRACT FROM AUTHOR]

The influence of proprioceptive feedback on muscle activity during isometric tasks is the subject of conflicting studies. We performed an isometric knee extension task experiment based on two common clinical tests for mobility and flexibility. The task was carried out at four preset angles of the knee, and we recorded from five muscles for two different hip positions. We applied muscle synergy analysis using nonnegative matrix factorization on surface electromyograph recordings to identify patterns in the data that changed with internal knee angle, suggesting a link between proprioception and muscle activity. We hypothesized that such patterns arise from the way proprioceptive and cortical signals are integrated in neural circuits of the spinal cord. Using the MIIND neural simulation platform, we developed a computational model based on current understanding of spinal circuits with an adjustable afferent input. The model produces the same synergy trends as observed in the data, driven by changes in the afferent input. To match the activation patterns from each knee angle and position of the experiment, the model predicts the need for three distinct inputs: two to control a nonlinear bias toward the extensors and against the flexors, and a further input to control additional inhibition of rectus femoris. The results show that proprioception may be involved in modulating muscle synergies encoded in cortical or spinal neural circuits. NEW & NOTEWORTHY The role of sensory feedback in motor control when limbs are held in a fixed position is disputed. We performed a novel experiment involving fixed position tasks based on two common clinical tests. We identified patterns of muscle activity during the tasks that changed with different leg positions and then inferred how sensory feedback might influence the observations. We developed a computational model that required three distinct inputs to reproduce the activity patterns observed experimentally. The model provides a neural explanation for how the activity patterns can be changed by sensory feedback. [ABSTRACT FROM AUTHOR]

Primitive reflexes are evident shortly after birth. Many of these reflexes disappear during postnatal development as part of the maturation of motor control. This study investigates the changes of connectivity related to sensory integration by spinal dI3 interneurons during the time in which the palmar grasp reflex gradually disappears in postnatal mice pups. Our results reveal an increase in GAD65/67-labeled terminals to perisomatic Vglut1-labeled sensory inputs contacting cervical and lumbar dI3 interneurons between postnatal day 3 and day 25. In contrast, there were no changes in the number of perisomatic Vglut1-labeled sensory inputs to lumbar and cervical dI3 interneurons other than a decrease between postnatal day 15 and day 25. Changes in postsynaptic GAD65/67-labeled inputs to dI3 interneurons were inconsistent with a role in the sustained loss of the grasp reflex. These results suggest a possible link between the maturation of hand grasp during postnatal development and increased presynaptic inhibition of sensory inputs to dI3 interneurons.

Locomotion is a complex process involving specific interactions between the central neural controller and the mechanical components of the system. The basic rhythmic activity generated by locomotor circuits in the spinal cord defines rhythmic limb movements and their central coordination. The operation of these circuits is modulated by sensory feedback from the limbs providing information about the state of the limbs and the body. However, the specific role and contribution of central interactions and sensory feedback in the control of locomotor gait and posture remain poorly understood. We use biomechanical data on quadrupedal locomotion in mice and recent findings on the organization of neural interactions within the spinal locomotor circuitry to create and analyse a tractable mathematical model of mouse locomotion. The model includes a simplified mechanical model of the mouse body with four limbs and a central controller composed of four rhythm generators, each operating as a state machine controlling the state of one limb. Feedback signals characterize the load and extension of each limb as well as postural stability (balance). We systematically investigate and compare several model versions and compare their behaviour to existing experimental data on mouse locomotion. Our results highlight the specific roles of sensory feedback and some central propriospinal interactions between circuits controlling fore and hind limbs for speed-dependent gait expression. Our models suggest that postural imbalance feedback may be critically involved in the control of swing-to-stance transitions in each limb and the stabilization of walking direction., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Cancer survivors rank sensorimotor disability among the most distressing, long-term consequences of chemotherapy. Disorders in gait, balance, and skilled movements are commonly assigned to chemotoxic damage of peripheral sensory neurons without consideration of the deterministic role played by the neural circuits that translate sensory information into movement. This oversight precludes sufficient, mechanistic understanding and contributes to the absence of effective treatment for reversing chemotherapy-induced disability. We rectified this omission through the use of a combination of electrophysiology, behavior, and modeling to study the operation of a spinal sensorimotor circuit in vivo in a rat model of chronic, oxaliplatin (chemotherapy)-induced neuropathy (cOIN). Key sequential events were studied in the encoding of propriosensory information and its circuit translation into the synaptic potentials produced in motoneurons. In cOIN rats, multiple classes of propriosensory neurons expressed defective firing that reduced accurate sensory representation of muscle mechanical responses to stretch. Accuracy degraded further in the translation of propriosensory signals into synaptic potentials as a result of defective mechanisms residing inside the spinal cord. These sequential, peripheral, and central defects compounded to drive the sensorimotor circuit into a functional collapse that was consequential in predicting the significant errors in propriosensory-guided movement behaviors demonstrated here in our rat model and reported for people with cOIN. We conclude that sensorimotor disability induced by cancer treatment emerges from the joint expression of independent defects occurring in both peripheral and central elements of sensorimotor circuits. [ABSTRACT FROM AUTHOR]

Correct operation of neuronal networks depends on the interplay between synaptic excitation and inhibition processes leading to a dynamic state termed balanced network. In the spinal cord, balanced network activity is fundamental for the expression of locomotor patterns necessary for rhythmic activation of limb extensor and flexor muscles. After spinal cord lesion, paralysis ensues often followed by spasticity. These conditions imply that, below the damaged site, the state of balanced networks has been disrupted and that restoration might be attempted by modulating the excitability of sublesional spinal neurons. Because of the widespread expression of inhibitory GABAergic neurons in the spinal cord, their role in the early and late phases of spinal cord injury deserves full attention. Thus, an early surge in extracellular GABA might be involved in the onset of spinal shock while a relative deficit of GABAergic mechanisms may be a contributor to spasticity. We discuss the role of GABA A receptors at synaptic and extrasynaptic level to modulate network excitability and to offer a pharmacological target for symptom control. In particular, it is proposed that activation of GABA A receptors with synthetic GABA agonists may downregulate motoneuron hyperexcitability (due to enhanced persistent ionic currents) and, therefore, diminish spasticity. This approach might constitute a complementary strategy to regulate network excitability after injury so that reconstruction of damaged spinal networks with new materials or cell transplants might proceed more successfully. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the effect of the spinal circuit of repetitive magnetic stimulation (rPMS) on the soleus muscle among healthy subjects., Methods: Nineteen healthy adults were included in this study. Intermittent rPMS was applied to the left soleus muscle for 20 minutes. We applied different intensity rPMS (high-intensity, low-intensity, and non-stimulation) in different three days. RI (reciprocal inhibition) from the tibialis anterior to the soleus muscle with an inter-stimulus interval (ISI) of 2ms and 20ms was assessed before, immediately after and 30 minutes at each session., Results: Two factor repeated measure ANOVA test showed a significant interaction (F 2,33  = 9.688, p < 0.001) between tasks and time in the RI ratio 2ms. Post-hoc analysis showed that RI ratio 2ms significantly differed from those immediately after, and 30 min after high-intensity rPMS (p = 0.001 and p = 0.003, respectively). A significant difference was observed between high-intensity rPMS and non-stimulation immediately after the stimulation (p = 0.003). However, no significant difference was found in the RI ratio 20ms between all the intensities (p > 0.05)., Conclusion: This study demonstrates that high-intensity rPMS can effectively modulate spinal circuits, as evidenced by the decreased RI in healthy individuals. This suggests the potential use of rPMS as a therapeutic intervention for patients with muscle weakness. Disinhibition of the RI may lead to a more effective contraction of the target muscle. This effect could be expected to strengthen the muscles and alleviate paralysis, making it a promising avenue for future research and clinical applications in the field of rehabilitation. Further investigation is warranted to explore the precise mechanisms underlying the observed effects and to optimize the parameters of rPMS for specific clinical populations., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Juntendo Medical Society.)

The pain experience depends on the relay of nociceptive signals from the spinal cord dorsal horn to higher brain centers. This function is ultimately achieved by the output of a small population of highly specialized neurons called projection neurons (PNs). Like output neurons in other central nervous system (CNS) regions, PNs are invested with a substantial axon collateral system that ramifies extensively within local circuits. These axon collaterals are widely distributed within and between spinal cord segments. Anatomical data on PN axon collaterals have existed since the time of Cajal, however, their function in spinal pain signaling remains unclear and is absent from current models of spinal pain processing. Despite these omissions, some insight on the potential role of PN axon collaterals can be drawn from axon collateral systems of principal or output neurons in other CNS regions, such as the hippocampus, amygdala, olfactory cortex, and ventral horn of the spinal cord. The connectivity and actions of axon collaterals in these systems have been well-defined and used to confirm crucial roles in memory, fear, olfaction, and movement control, respectively. We review this information here and propose a framework for characterizing PN axon collateral function in the dorsal horn. We highlight that experimental approaches traditionally used to delineate axon collateral function in other CNS regions are not easily applied to PNs because of their scarcity relative to spinal interneurons (INs), and the lack of cellular organization in the dorsal horn. Finally, we emphasize how the rapid development of techniques such as viral expression of optogenetic or chemogenetic probes can overcome these challenges and allow characterization of PN axon collateral function. Obtaining detailed information of this type is a necessary first step for incorporation of PN collateral system function into models of spinal sensory processing.

Abstract A putative spinal circuit with convergent inputs facilitating human wrist flexors has been recently described. This study investigated how central nervous system lesions may affect this pathway. We measured the flexor carpi radialis H-reflex conditioned with stimulation above motor threshold to the extensor carpi radialis at different intervals in fifteen patients with stroke and nine with spinal cord injury. Measurements after stroke revealed a prolonged facilitation of the H-reflex, which replaced the later suppression seen in healthy subjects at longer intervals (30–60 ms). Measurements in patients with incomplete spinal cord injury at cervical level revealed heterogeneous responses. Results from patients with stroke could represent either an excessive facilitation or a loss of inhibition, which may reflect the development of spasticity. Spinal cord injury results possibly reflect damage to the segmental interneuron pathways. We report a straightforward method to assess changes to spinal circuits controlling wrist flexors after central nervous system lesion.

The pain experience depends on the relay of nociceptive signals from the spinal cord dorsal horn to higher brain centers. This function is ultimately achieved by the output of a small population of highly specialized neurons called projection neurons (PNs). Like output neurons in other central nervous system (CNS) regions, PNs are invested with a substantial axon collateral system that ramifies extensively within local circuits. These axon collaterals are widely distributed within and between spinal cord segments. Anatomical data on PN axon collaterals have existed since the time of Cajal, however, their function in spinal pain signaling remains unclear and is absent from current models of spinal pain processing. Despite these omissions, some insight on the potential role of PN axon collaterals can be drawn from axon collateral systems of principal or output neurons in other CNS regions, such as the hippocampus, amygdala, olfactory cortex, and ventral horn of the spinal cord. The connectivity and actions of axon collaterals in these systems have been well-defined and used to confirm crucial roles in memory, fear, olfaction, and movement control, respectively. We review this information here and propose a framework for characterizing PN axon collateral function in the dorsal horn. We highlight that experimental approaches traditionally used to delineate axon collateral function in other CNS regions are not easily applied to PNs because of their scarcity relative to spinal interneurons (INs), and the lack of cellular organization in the dorsal horn. Finally, we emphasize how the rapid development of techniques such as viral expression of optogenetic or chemogenetic probes can overcome these challenges and allow characterization of PN axon collateral function. Obtaining detailed information of this type is a necessary first step for incorporation of PN collateral system function into models of spinal sensory processing. [ABSTRACT FROM AUTHOR]

The excitability of resting motoneurons increases following spinal cord injury (SCI). The extent to which motoneuron excitability changes during voluntary muscle activity in humans with SCI, however, remains poorly understood. To address this question, we measured F waves by using supramaximal electrical stimulation of the ulnar nerve at the wrist and cervicomedullary motor-evoked potentials (CMEPs) by using high-current electrical stimulation over the cervicomedullary junction in the first dorsal interosseous muscle at rest and during 5 and 30% of maximal voluntary contraction into index finger abduction in individuals with chronic cervical incomplete SCI and aged-matched control participants. We found higher persistence (number of F waves present in each set) and amplitude of F waves at rest in SCI compared with control participants. With increasing levels of voluntary contraction, the amplitude, but not the persistence, of F waves increased in both groups but to a lesser extent in SCI compared with control participants. Similarly, the CMEP amplitude increased in both groups but to a lesser extent in SCI compared with controls. These results were also found at matched absolutely levels of electromyographic activity, suggesting that these changes were not related to decreases in voluntary motor output after SCI. F-wave and CMEP amplitudes were positively correlated across conditions in both groups. These results support the hypothesis that the responsiveness of the motoneuron pool during voluntary activity decreases following SCI, which could alter the generation and strength of voluntary muscle contractions. [ABSTRACT FROM AUTHOR]

Visceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here, we conducted focal colorectal distention (fCRD) to drive both visceromotor responses (VMRs) and aversion. We first found that spinal CCK neurons were necessary for noxious fCRD to drive both VMRs and aversion under naive conditions. We next showed that spinal VGLUT3 neurons mediate visceral allodynia, whose ablation caused loss of aversion evoked by low-intensity fCRD in mice with gastrointestinal (GI) inflammation or spinal circuit disinhibition. Importantly, these neurons were dispensable for driving sensitized VMRs under both inflammatory and central disinhibition conditions. Anatomically, a subset of VGLUT3 neurons projected to parabrachial nuclei, whose photoactivation sufficiently generated aversion in mice with GI inflammation, without influencing VMRs. Our studies suggest the presence of different spinal substrates that transmit nociceptive versus affective dimensions of visceral sensory information. • Focal colorectal distention (fCRD) can drive both visceromotor reflexes and aversion • Spinal CCK neurons drive acute visceromotor reflexes and aversion by noxious fCRD • Spinal VGLUT3 lineage neurons drive fCRD-evoked allodynia in mice with colitis • Spinal VGLUT3-negative neurons sufficiently drive sensitized visceromotor reflexes Qi et al. uncover a spinal substrate that is required to drive aversion evoked by low-intensity colorectal distension in mice with gastrointestinal inflammation, but which is dispensable for visceromotor responses, thereby calling for a revisit on how to measure the affective component of visceral pain. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that both α and γ motoneurons are active during movement and posture, but how does the central motor system coordinate the α-γ controls in these tasks remains sketchy due to lack of in vivo data. Here a computational model of α-γ control of muscles and spindles was used to investigate α-γ integration and coordination for movement and posture. The model comprised physiologically realistic spinal circuitry, muscles, proprioceptors, and skeletal biomechanics. In the model, we divided the cortical descending commands into static and dynamic sets, where static commands (static α and γ) were for posture maintenance and dynamic commands (dynamic α and γ) were responsible for movement. We matched our model to human reaching movement data by straightforward adjustments of descending commands derived from either minimal-jerk trajectories or human EMGs. The matched movement showed smooth reach-to-hold trajectories qualitatively close to human behaviors, and the reproduced EMGs showed the classic tri-phasic patterns. In particular, the function of dynamic γ was to gate the αd command at the propriospinal neurons (PN) such that antagonistic muscles can accelerate or decelerate the limb with proper timing. Independent control of joint position and stiffness could be achieved by adjusting static commands. Deefferentation in the model indicated that accurate static commands of static α and γ are essential to achieve stable terminal posture precisely, and that the dynamic γ command is as important as the dynamic α command in controlling antagonistic muscles for desired movements. Deafferentation in the model showed that losing proprioceptive afferents mainly affected the termination position of movement, similar to the abnormal behaviors observed in human and animals. Our results illustrated that tuning the simple forms of α-γ commands can reproduce a range of human reach-to-hold movements, and it is necessary to coordinate the set of α-γ descending commands for accurate and stable control of movement and posture.

The dynamic interaction of limb segments during movements that involve multiple joints creates torques in one joint due to motion about another. Evidence shows that such interaction torques are taken into account during the planning or control of movement in humans. Two alternative hypotheses could explain the compensation of these dynamic torques. One involves the use of internal models to centrally compute predicted interaction torques and their explicit compensation through anticipatory adjustment of descending motor commands. The alternative, based on the equilibrium-point hypothesis, claims that descending signals can be simple and related to the desired movement kinematics only, while spinal feedback mechanisms are responsible for the appropriate creation and coordination of dynamic muscle forces. Partial supporting evidence exists in each case. However, until now no model has explicitly shown, in the case of the second hypothesis, whether peripheral feedback is really sufficient on its own for coordinating the motion of several joints while at the same time accommodating intersegmental interaction torques. Here we propose a minimal computational model to examine this question. Using a biomechanics simulation of a two-joint arm controlled by spinal neural circuitry, we show for the first time that it is indeed possible for the neuromusculoskeletal system to transform simple descending control signals into muscle activation patterns that accommodate interaction forces depending on their direction and magnitude. This is achieved without the aid of any central predictive signal. Even though the model makes various simplifications and abstractions compared to the complexities involved in the control of human arm movements, the finding lends plausibility to the hypothesis that some multijoint movements can in principle be controlled even in the absence of internal models of intersegmental dynamics or learned compensatory motor signals.

As our understanding of motor circuit function increases, our need to understand how circuits form to ensure proper function becomes increasingly important. Recently, deleted in colorectal cancer ( DCC) has been shown to be important in the development of spinal circuits necessary for gait. Importantly, humans with mutation in DCC show mirror movement disorders pointing to the significance of DCC in the development of spinal circuits for coordinated movement. Although DCC binds a number of ligands, the intracellular signaling cascade leading to the aberrant spinal circuits remains unknown. Here, we show that the non-catalytic region of tyrosine kinase adaptor ( NCK) proteins 1 and 2 are distributed in the developing spinal cord. Using dissociated dorsal spinal neuron cultures we show that NCK proteins are necessary for the outgrowth and growth cone architecture of DCC+ve dorsal spinal neurons. Consistent with a role for NCK in DCC signaling, we show that loss of NCK proteins leads to a reduction in the thickness of TAG1+ve commissural bundles in the floor plate and loss of DCC mRNA in vivo. We suggest that DCC signaling functions through NCK1 and NCK2 and that both proteins are necessary for the establishment of normal spinal circuits necessary for gait. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that both (#945; and #947; motoneurons are active during movement and posture, but how does the central motor system coordinate the #945;-#947; controls in these tasks remains sketchy due to lack of in vivo data. Here a computational model of #945;-#947; control of muscles and spindles was used to investigate #945;-#947; integration and coordination for movement and posture. The model comprised physiologically realistic spinal circuitry, muscles, proprioceptors, and skeletal biomechanics. In the model, we divided the cortical descending commands into static and dynamic sets, where static commands (αs and γs) were for posture maintenance and dynamic commands (αd and γd) were responsible for movement. We matched our model to human reaching movement data by straightforward adjustments of descending commands derived from either minimal-jerk trajectories or human EMGs. The matched movement showed smooth reach-to-hold trajectories qualitatively close to human behaviors, and the reproduced EMGs showed the classic tri-phasic patterns. In particular, the function of γd was to gate the αd command at the propriospinal neurons (PN) such that antagonistic muscles can accelerate or decelerate the limb with proper timing. Independent control of joint position and stiffness could be achieved by adjusting static commands. Deefferentation in the model indicated that accurate static commands of αs and γs are essential to achieve stable terminal posture precisely, and that the γd command is as important αs the αd command in controlling antagonistic muscles for desired movements. Deafferentation in the model showed that losing proprioceptive afferents mainly affected the termination position of movement, similar to the abnormal behaviors observed in human and animals. Our results illustrated that tuning the simple forms of #945;-#947; commands can reproduce a range of human reach-to-hold movements, and it is necessary to coordinate the set of #945;-#947; descending commands for accurate and stable control of movement and posture. [ABSTRACT FROM AUTHOR]

In humans, a chronic spinal cord injury (SCI) impairs the excitability of pathways mediating early flexor reflexes and increases the excitability of late, long-lasting flexor reflexes. We hypothesized that in individuals with SCI, locomotor training will alter the behavior of these spinally mediated reflexes. Nine individuals who had either chronic clinically motor complete or incomplete SCI received an average of 44 locomotor training sessions. Flexor reflexes, elicited via sural nerve stimulation of the right or left leg, were recorded from the ipsilateral tibialis anterior (TA) muscle before and after body weight support (BWS)-assisted treadmill training. The modulation pattern of the ipsilateral TA responses following innocuous stimulation of the right foot was also recorded in 10 healthy subjects while they stepped at 25% BWS to investigate whether body unloading during walking affects the behavior of these responses. Healthy subjects did not receive treadmill training. We observed a phase-dependent modulation of early TA flexor reflexes in healthy subjects with reduced body weight during walking. The early TA flexor reflexes were increased at heel contact, progressively decreased during the stance phase, and then increased throughout the swing phase. In individuals with SCI, locomotor training induced the reappearance of early TA flexor reflexes and changed the amplitude of late TA flexor reflexes during walking. Both early and late TA flexor reflexes were modulated in a phase-dependent pattern after training. These new findings support the adaptive capability of the injured nervous system to return to a prelesion excitability and integration state. [ABSTRACT FROM AUTHOR]

The dynamic interaction of limb segments during movements that involve multiple joints creates torques in one joint due to motion about another. Evidence shows that such interaction torques are taken into account during the planning or control of movement in humans. Two alternative hypotheses could explain the compensation of these dynamic torques. One involves the use of internal models to centrally compute predicted interaction torques and their explicit compensation through anticipatory adjustment of descending motor commands. The alternative, based on the equilibrium-point hypothesis, claims that descending signals can be simple and related to the desired movement kinematics only, while spinal feedback mechanisms are responsible for the appropriate creation and coordination of dynamic muscle forces. Partial supporting evidence exists in each case. However, until now no model has explicitly shown, in the case of the second hypothesis, whether peripheral feedback is really sufficient on its own for coordinating the motion of several joints while at the same time accommodating intersegmental interaction torques. Here we propose a minimal computational model to examine this question. Using a biomechanics simulation of a two-joint arm controlled by spinal neural circuitry, we show for the first time that it is indeed possible for the neuromusculoskeletal system to transform simple descending control signals into muscle activation patterns that accommodate interaction forces depending on their direction and magnitude. This is achieved without the aid of any central predictive signal. Even though the model makes various simplifications and abstractions compared to the complexities involved in the control of human arm movements, the finding lends plausibility to the hypothesis that some multijoint movements can in principle be controlled even in the absence of internal models of intersegmental dynamics or learned compensatory motor signals. [ABSTRACT FROM AUTHOR]

From swimming to walking and flying, animals have evolved specific locomotor strategies to thrive in different habitats. All types of locomotion depend on the integration of motor commands and sensory information to generate precisely coordinated movements. Cerebrospinal-fluid-contacting neurons (CSF-cN) constitute a vertebrate sensory system that monitors CSF composition and flow. In fish, CSF-cN modulate swimming activity in response to changes in pH and bending of the spinal cord; however, their role in mammals remains unknown. We used mouse genetics to study their function in quadrupedal locomotion. We found that CSF-cN are directly integrated into spinal motor circuits. The perturbation of CSF-cN function does not affect general motor activity nor the generation of locomotor rhythm and pattern but results in specific defects in skilled movements. These results identify a role for mouse CSF-cN in adaptive motor control and indicate that this sensory system evolved a novel function to accommodate the biomechanical requirements of limb-based locomotion. [Display omitted] • CSF-cN are evolutionary conserved components of mouse spinal sensorimotor circuits • Elimination of CSF-cN compromises adaptive motor control • The cilium is required for CSF-cN function • Pkd2l1 is dispensable for CSF-cN function in mice Cerebrospinal fluid-contacting neurons (CSF-cN) represent an evolutionary conserved vertebrate interoceptive system relaying sensory information from the CSF to spinal motor circuits. This study reveals CSF-cN's role in mammalian motor control where they contribute to orchestrate the precise execution of movements required for skilled locomotion. [ABSTRACT FROM AUTHOR]

Body weight-supported (BWS) robotic-assisted step training on a motorized treadmill is utilized with the aim to improve walking ability in people after damage to the spinal cord. However, the potential for reorganization of the injured human spinal neuronal circuitry with this intervention is not known. The objectives of this study were to determine changes in the soleus H-reflex modulation pattern and activation profiles of leg muscles during stepping after BWS robotic-assisted step training in people with chronic spinal cord injury (SCI). Fourteen people who had chronic clinically complete, motor complete, and motor incomplete SCI received an average of 45 training sessions, 5 days per week, 1 h per day. The soleus H-reflex was evoked and recorded via conventional methods at similar BWS levels and treadmill speeds before and after training. After BWS robotic-assisted step training, the soleus H-reflex was depressed at late stance, stance-to-swing transition, and swing phase initiation, allowing a smooth transition from stance to swing. The soleus H-reflex remained depressed at early and mid-swing phases of the step cycle promoting a reciprocal activation of ankle flexors and extensors. The spinal reflex circuitry reorganization was, however, more complex, with the soleus H-reflex from the right leg being modulated either in a similar or in an opposite manner to that observed in the left leg at a given phase of the step cycle after training. Last, BWS robotic-assisted step training changed the amplitude and onset of muscle activity during stepping, decreased the step duration, and improved the gait speed. BWS robotic-assisted step training reorganized spinal locomotor neuronal networks promoting a functional amplitude modulation of the soleus H-reflex and thus step progression. These findings support that spinal neuronal networks of persons with clinically complete, motor complete, or motor incomplete SCI have the potential to undergo an endogenous-mediated reorganization, and improve spinal reflex function and walking function with BWS robotic-assisted step training. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To establish the modulation pattern of reciprocal inhibition and presynaptic inhibition of soleus Ia afferents during robot-assisted stepping in healthy subjects. Methods: During stepping, the soleus H-reflex was conditioned by percutaneous stimulation of the ipsilateral common peroneal nerve with a single pulse at stimulation intensities that ranged from 0.9 to 1.2 TA M-wave motor thresholds across subjects. To control for movement of recording and stimulating electrodes, a supramaximal stimulus 80ms after the conditioned and/or unconditioned H-reflexes was delivered to the posterior tibial nerve. The short (2, 3, 4ms) and long (60–80ms) conditioning-test intervals at which the largest amount of reflex depression was observed with the subjects seated were utilized during stepping. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. Results: Reciprocal inhibition exerted from flexor group I afferents onto soleus motoneurons was decreased at mid-stance and increased and late-stance and throughout the swing phase. Presynaptic inhibition of soleus Ia afferents was increased at heel strike and decreased at late-stance and early swing phases. Conclusion: Reciprocal inhibition between ankle antagonistic muscles and presynaptic inhibition of soleus Ia afferents are modulated in a similar pattern to that reported during walking on a treadmill with full weight bearing and without robot-assisted leg movement. Significance: The activity of spinal interneuronal circuits engaged in patterned locomotor activity supports a reciprocal gait pattern during robot-assisted stepping in healthy humans. [Copyright &y& Elsevier]